外膜囊泡介导的碳青霉烯类抗生素耐药机制

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis Pub Date : 2025-04-30 DOI:10.1016/j.micpath.2025.107654

Dan Zhou , Xiaoyu Yang , Yuhong Gao , Rui Zheng

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引用次数: 0

摘要

革兰氏阴性菌中碳青霉烯耐药的流行率不断上升，提出了一个关键的治疗挑战，迫切需要阐明新的耐药机制。本文系统地综述了外膜囊泡（omv）作为碳青霉烯耐药的多功能介质的新作用，并综合了其生物学特性和机制贡献的最新进展。通过对β-内酰胺酶传播途径的综合分析，我们证明了omv是细胞外载体，通过酶货物递送促进抗生素降解，同时也是抗性决定因素的遗传传播载体。至关重要的是，omv通过双重机制在增强细菌存活方面表现出功能性的多功能性：结构上，通过促进生物膜基质的形成，建立抗生素保护的生态位；免疫上，通过调节损害微生物清除的宿主-病原体相互作用。该综述进一步确定了omv介导的抗生素隔离和竞争结合是未被充分认识的耐药性放大器。这些见解完善了我们对耐药性进化的理解，并揭示了OMV生物发生途径是有希望的治疗靶点。该合成确立了omv在碳青霉烯耐药结构中的核心作用，为制定针对多重耐药感染的对策提供了战略框架。

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The mechanism of outer membrane vesicle-mediated resistance to carbapenem antibiotics

The escalating prevalence of carbapenem resistance in Gram-negative bacteria presents a critical therapeutic challenge, demanding urgent elucidation of novel resistance mechanisms. This review systematically examines the emerging role of outer membrane vesicles (OMVs) as multifunctional mediators of carbapenem resistance, synthesizing recent advances in understanding their biological properties and mechanistic contributions. Through comprehensive analysis of β-lactamase dissemination pathways, we demonstrate that OMVs are extracellular vectors facilitating antibiotic degradation through enzymatic cargo delivery while concurrently acting as genetic transmission vehicles for resistance determinants. Crucially, OMVs exhibit functional versatility in enhancing bacterial survival via dual mechanisms: structurally, by promoting biofilm matrix formation that establishes antibiotic-protected niches, and immunologically, through modulation of host-pathogen interactions that impair microbial clearance. The review further identifies OMV-mediated antibiotic sequestration and competitive binding as underappreciated resistance amplifiers. These insights refine our understanding of resistance evolution and reveal OMV biogenesis pathways as promising therapeutic targets. This synthesis establishes OMVs as central players in carbapenem resistance architecture, providing a strategic framework for developing countermeasures against multidrug-resistant infections.

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来源期刊

Microbial pathogenesis 医学-免疫学

CiteScore

7.40

自引率

2.60%

发文量

472

审稿时长

56 days

期刊介绍： Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)